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• Electroencephalography (EEG) remains a pivotal investigation in Autoimmune Encephalitis (AE). • The EEG changes in Autoimmune Encephalitis (AE) are: abnormal background activity (82 %), epileptiform discharges (25.6 %), extreme delta brush (EDB) (35.8 %), frontal intermittent rhythmic delta activity (FIRDA) (20.5 %) and electrographic seizures (30.7 %). Eight (11.9 %) patients developed epilepsy. • Abnormal background and epileptiform discharges on EEG correlated with modified Rankin Scale (mRS) >2 (p = 0.015) and abnormal MRI (p = 0.017). • Late onset AE, seronegative status, status epilepticus and late initiation of immunotherapy were predictors in development of epilepsy. An abnormal EEG is pivotal in diagnosis, exclusion of mimickers and prognosticating epilepsy in Autoimmune Encephalitis (AE). However, little is known about the short and long term electroencephalographic outcomes and predictors of epilepsy in AE. This study aims to describe the seizure characteristics and electrophysiological markers of various AE subtypes and assess the clinical and electrophysiological predictors of autoimmune epilepsy. Clinical features and EEGs in 74 patients (acute phase=39 and post-acute phase defined after a minimum eight weeks after acute phase=35) of AE fulfilling the proposed criteria were reviewed in their respective acute phases and at six months follow-up. The mean age of presentation (N = 74, 45 females) was 21.8 (21.8 ± 17.0) years. 38 (51 %) patients were <18 years. Seizures were present in 55 (74 %) patients with poor response to ASMs (p = 0.039). 39 (52.7 %) EEGs were abnormal in acute phase. Anti-NMDAR AE had most frequently abnormal EEG (63.4 %). Poor background reactivity and theta range slowing were most common abnormalities. FIRDA, EDB and delta range slowing were seen in seropositive AE (P = 0.003). Mutism, psychiatric features and incontinence correlated with abnormal EEG (p = 0.013, p = 0.028 and p = 0.025). Background slowing and epileptiform discharges predicted worse cognitive scores at follow-up (p = 0.012). Eight (11.9 %) patients developed epilepsy. Status epilepticus at presentation (p = 0.009), seronegative status (p = 0.0020), delayed initiation of immunotherapy (p = 0.012), abnormal MRI (p = 0.003) and abnormal EEG (p = 0.004) at onset indicate development of autoimmune epilepsy FIRDA, EDB and delta range slowing with refractory seizures suggest AE. Epileptiform abnormalities, status epilepticus and seronegativity predict autoimmune epilepsy. [ABSTRACT FROM AUTHOR]

• One of the largest cohorts of operated cases exploring the role MEG in prediction of seizure outcome. • Concordance of MEG with resection cavity was associated with good post-operative outcomes with a sensitivity of 83 %. • The sensitivity of MEG ranged from 83 to 70 from 6 months to 5 years follow up, whereas specificity was 68 % & 40 %. • Level 1 concordance was associated with a good outcome in 78% vs 66 % in temporal vs extratemporal at 6 months follow-up. • No definite association was noted between MEG cluster characteristics and outcome except cluster strength. Study assessed the role of MSI in predicting the post-operative seizure outcome. This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed. A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up. The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cell (MSC) therapy for diabetic neuropathy (DN) has been extensively researched in vitro and in pre-clinical studies; however, the clinical scenario thus far has been disappointing. Temporary recovery, a common feature of these studies, indicates that either the retention of transplanted cells deteriorates with time or recovery of supportive endogenous cells, such as bone marrow-derived MSCs (BM-MSCs), does not occur, requiring further replenishment. In DN, BM-MSCs are recognized mediators of Schwann cell regeneration, and we have earlier shown that they suffer impairment in the pre-neuropathy stage. In this study, we attempted to further elucidate the mechanisms of functional recovery by focusing on changes occurring at the cellular level in the sciatic nerve, in conjunction with the biodistribution and movement patterns of the transplanted cells, to define the interval between doses. We found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture. Thus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN. [ABSTRACT FROM AUTHOR]

• Tract-specific myelopathy has not been reported previously in Myelin oligodendrocyte associated disorders (MOGAD) • Our case demonstrates multi-level patchy tract-specific involvement of the spinal cord in a proven case of MOGAD. • Awareness of this entity can reduce unnecessary investigations, leading to appropriate and timely management. [ABSTRACT FROM AUTHOR]

• Epilepsy is associated with alteration in large-scale functional networks. • We evaluated MEG based multi-band difference in resting sate brain networks between TLE subjects who underwent epilepsy surgery. • TLE-MTS patients with good seizure-outcome demonstrated increased global GT measures in the broadband compared to patients with poor seizure outcome. • Non–MTS lesional-TLE demonstrated distinct pattern of network connectivity in good and poor outcome groups. • MEG based resting state network analysis using graph theory helps in predicting surgical outcome and could emerge as a novel bio-marker in epilepsy surgery. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the utility of magnetoencephalography in presurgical planning and in predicting post-surgical seizure outcome.Methods: This study included a cohort of 231 children (1-18 years) with focal drug-resistant epilepsy who underwent MEG as a part of their presurgical workup. Characteristics of MEG observations were described in all children. The concordance and agreement of Magnetic Source Imaging (MSI) of interictal discharges (IED) was estimated with either of the 3 subgroups - MRI lesion; presumed epileptogenic zone (EZ); or resection cavity. In operated children group, MEG dipole characteristics between good and poor outcome groups were assessed.Results: A total of 153 cases (66.2%) showed frequent IEDs (60 spikes/60 min). Of the 173 cases where MSI showed clusters (74.9%), 151 had lesions and 22 were non-lesional. amongst patients with lesional epilepsy and MEG clusters, class I concordance (MEG localization either completely included or overlapped at least 60% with the MRI lesion) was seen in 60.92% with a Cohen's kappa of 0.608. In non-lesional epilepsy, class I concordance of MEG with presumed EZ was found in (81.81%) with an agreement of 0.317. Fifty-three children underwent surgery of whom 39 (73.58%) showed a good outcome (Engel I). In operated children, concordance between MEG focus and resection cavity was observed in 23 (58.97%) with good outcome and in 12 (86.72%) with poor outcome with no significant difference (p>0.05). However, MEG cluster regular organization and clusterectomy are associated with good seizure outcome postoperatively (p< 0.05). Presence of scatters were associated with poor outcome (p<0.05) in children with focal cortical dysplasia.Conclusions: MEG provides useful information that can serve as a biomarker for prognosticating the surgical outcome in paediatric epilepsy. Cluster removal and regular cluster organization shows predictive power in post-surgical prognostication in children and the presence of scatters predicts poor outcome in children with focal cortical dysplasia. [ABSTRACT FROM AUTHOR]

• Neuropathological spectrum of DRE employing the latest ILAE consensus classification (largest study from a single institute). • Hippocampal sclerosis, focal cortical dysplasia and neoplasms are the most frequent pathologies. • Pathological evaluation useful in identifying additional unsuspected pathologies in few. • Radiopathological concordance seen in majority. • Use of standardized pathological criteria is essential for uniformity. Neuropathology of drug resistant epilepsy (DRE) has direct bearing on the clinical outcome. Classification of the most common pathologies, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) have undergone several revisions and studies on the surgical pathology of DRE employing the updated ILAE classification are scarce. Here, we report the neuropathological spectrum of 482 surgically treated cases of DRE from a single institute using the latest ILAE classifications along with clinicoradiologic correlation. Majority of the cases (324, 67.2%) had temporal lobe epilepsy (TLE), with 158 (32.8%) having extratemporal seizure focus. Among TLE, HS was most common (n = 208, 64.2%), followed by neoplasms (42, 13%), FCD (26, 8%) and dual pathology (23, 7%). Less frequent were vascular malformations (cavernoma-3, arteriovenous malformation-1), mild malformation of cortical development (mMCD, 3), gliotic lesions (5), cysticercosis (2), double pathology (2) and polymicrogyria (1). Among extratemporal epilepsies, FCD was most common (46, 29.1%), followed by neoplasms (29, 18.3%), gliotic lesions (27, 17.1%), Rasmussen encephalitis (18, 11.4%), hypothalamic hamartoma (12, 7.6%), malformations of cortical development (10, 6.3%) and vascular malformations (6, 3.8%). Less frequent were double pathology (2, cysticercosis + FCD type IIb, DNET + FCD type IIb), mMCD (2), cysticercosis (1) and dual pathology (1). No underlying pathology was detected in 12 cases (2.5%). Radiopathological concordance was noted in 83%. In 36 cases (7.5%), histopathology detected an unsuspected second pathology that included FCD type III (n = 16) dual pathology (n = 18) and double pathology (n = 2). Further, in four MRI negative cases, histopathology was required for a conclusive diagnosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Aging & Parkinson's disease cause neuron loss; may alter nigral neuronal structure. • Dendritic arborisation was evaluated in aging human nigra by Golgi-Kopsch protocol. • Synaptophysin & synaptotagmin-11 expression; studied as a sign of synaptic anomaly. • Subtle drop in dendrite length & intersections imply reduced structural complexity. • Mild decline in proteins with age hint at a parallel fall in synaptic vesicular flow. Abstract The protein α-synuclein, a major component of Lewy bodies in nigral neurons of aged and Parkinson's disease (PD) patients, normally co-localizes with synaptophysin and regulates the pool of synaptic vesicles. Our earlier study on substantia nigra pars compacta (SNpc) in an Asian-Indian population, demonstrated an age-associated linear but non-logarithmic increase in soluble α-synuclein without any loss of nigral neurons. Another distinctive finding was the presence of activated microglia in the ventrolateral region of the aged nigra, suggesting sub-threshold neurodegeneration. Since microglia prune dendrites, we evaluated the alterations in dendritic arborisation in the SNpc from autopsied midbrains of Asian-Indians through aging, using Golgi-Kopsch protocol. Further, we evaluated the expression of synaptic proteins, synaptophysin and synaptotagmin-11 as parallel markers of synaptic transmission anomalies. The dendritic arborization pattern was typical of large multipolar neurons. A subtle but non-significant decline in parameters like dendritic length and number of intersections was noted. Thus, the alterations were milder than those reported in PD. In the neurons of the young (till 10 years), faint cytoplasmic immunoreactivity of synaptic proteins was noted. In the adults and elderly, it was membrane-bound or appeared as punctae within neuropil. Both proteins showed a slight age-related decline, suggesting a mild decrease in the synaptic vesicular traffic, affecting the dopamine transmission with age that may manifest as minor motor disabilities in the elderly. Mapping the differences in synaptic profiles in differentially susceptible ethnic populations, could reveal interesting insights. Thus, nigra of aged individuals and PD patients share pathogenic features that differ in magnitude. [ABSTRACT FROM AUTHOR]

Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in understanding of its pathobiology. Advances in science have led us on the trail of the virus in the host, but the sanctuaries in which the virus remains hidden for its survival are unknown. Insights into host-pathogen interactions have facilitated evolving immunologic therapeutic strategies, though we are far from a cure. Most of the present-day knowledge has evolved from in vitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much remains to be unraveled about this elusive virus. This review attempts to re-examine the current advances in understanding of the pathobiology of the rabies virus that modulate the diagnosis, treatment, and prevention of this fatal disease. [ABSTRACT FROM AUTHOR]

Abstract: Sirenomelia, a developmental defect involving the caudal region of the body, is associated with several internal visceral anomalies. We report a detailed spectrum of anomalies in an autopsy study of four fetuses with sirenomelia (gestational ages – 20, 21, 22.4, and 22.5 weeks). Three of the fetuses had single umbilical artery, with genitourinary and gastrointestinal anomalies. Central nervous system anomalies were evident in two of the fetuses, with alobar holoprosencephaly in one and lumbar meningomyelocele in another. The most common gastrointestinal anomaly was blind ended gut (imperforate anus), while esophageal atresia and omphalocele were noted in one case each. Renal hypoplasia was seen in two fetuses, renal agenesis in one and cystic renal dysplasia was noted in one case. Literature regarding pathogenesis of this condition is briefly discussed. [Copyright &y& Elsevier]

• Report of twenty nine cases of CNS demyelination with close temporal association to COVID-19 vaccination. • Clinical presentation is heterogenous, including myelitis, optic neuritis, ADEM, brainstem demyelination and multiaxial involvement. • Most prevalent antibody in postvaccinial cases is the antibody against MOG antigen. • As compared to the controls, postvaccinial demyelination cases have significantly higher encephalopathy features, CSF pleocytosis and raised CSF protein. ChAdOx1-S (Covishield™/Vaxzervria, AstraZeneca) and BBV152 (Covaxin) SARS-CoV-2 vaccines are proven to be safe and effective, but rare complications have been reported. To describe reports of central nervous system (CNS) demyelination following ChAdOx1-S and BBV152 vaccinations. We report 29 (17 female; mean 38 years) cases of CNS demyelination; twenty-seven occurred in temporal association with ChAdOx1-S vaccine; two in association with BBV152 vaccine. Eleven patients had presentation with myelitis, six patients developed optic neuritis, five had acute demyelinating encephalomyelitis, three presented with brainstem demyelination, and four had multiaxial involvement. Myelin oligodendrocyte glycoprotein (MOG) antibodies were positive in ten patients. One patient with ADEM and tumefactive demyelinating lesions died after a prolonged intensive care unit stay and superimposed infection. As compared to the control group (87); the postvaccinial cases were found to have a significantly higher mean age, presence of encephalopathy (p value:0.0007), CSF pleocytosis (p value: 0.0094) and raised CSF protein (p value: 0.0062). It is difficult to establish a causal relationship between vaccination and neurological adverse events such as demyelination. The temporal association with the vaccination and the presence of MOG antibodies raises the possibility of an immunogenic process triggered by the vaccine in susceptible individuals. [ABSTRACT FROM AUTHOR]

• Phase amplitude coupling shows distinct patterns of cross frequency interactions in healthy controls and temporal lobe epilepsy patients even during resting state records. • SVM shows high classification potential to classify healthy controls from temporal lobe epilepsy patients and to lateralize epileptic focus in temporal lobe epilepsy using phase amplitude coupling. • Low gamma (30–80 Hz) interactions with lower frequency band (1–8 Hz) can identify hemisphere with epileptic focus in unilateral drug resistant temporal lobe epilepsy in resting state MEG even in the lack of ictal or interictal discharges. • Phase amplitude coupling in resting state records can supplement video-EEG in the pre-surgical evaluation of drug resistant unilateral temporal lobe epilepsy. Lateralization of seizure focus in temporal lobe epilepsy (TLE) is a prime step in pre-surgical evaluation requiring prolonged seizure monitoring using video EEG and manual inspection of recordings. This study uses phase amplitude coupling (PAC) in resting state magnetoencephalography to automatically lateralize TLE focus. Fifty-four patients with drug resistant TLE and 21 healthy controls who underwent MEG were considered for the study. Classification was carried out for PAC calculated for source transformed resting state of controls vs left TLE (LTLE)/right TLE (RTLE) and LTLE vs RTLE between beta, low-gamma and high-gamma as high frequency (HF) bands and low frequency (LF) 1–13 Hz, with decision tree (DT), support vector machines (SVM) and naïve Bayes with feature selection by chi-square test. Further, lateralization classification was also calculated with LF sub-bands (delta, theta, alpha). PAC was higher in the TLE compared to controls. LTLE and RTLE showed differences in low gamma-alpha and high gamma-delta coupling (p < 0.05). Accuracy was highest with SVM between controls and LTLE in the low gamma-LF (92.92%, AUC-1), between controls and RTLE in DT and SVM (93.54%, AUC-0.97, 1) in the low gamma-LF band and in low gamma-delta band in SVM (92.04%, AUC-1) between LTLE and RTLE. PAC shows distinct patterns of coupling in each subject group. Feature selection showed involvement of major network hubs and resting state networks. SVM showed best classification potential in the low gamma band. PAC in resting state MEG can supplement pre-surgical evaluation in drug resistant TLE. [ABSTRACT FROM AUTHOR]

• Exclusive emesis without hiccups is seen in MOGAD patients. • Exclusive emesis without hiccups occurs in patients of ADEM, Optic neuritis and Brainstem syndrome in MOGAD. • There is a predilection of anterior medulla, pons and MCP involvement in MOGAD that disrupts the emesis circuit. • Emesis with hiccups → AQP4 NMO; Emesis without hiccups → MOGAD. Exclusive emesis has been observed in few patients of MOG-associated disorder (MOGAD). To study the occurrence of emesis in patients of Demyelinating disorders and determine their clinical and radiological features. Medical records of 551 patients of CNS demyelinating disorders were reviewed. Exclusive emesis without hiccups was observed in 1 (0.1%) patient of MS, 17 (6.5%) patients of MOGAD while none were observed in patients of AQP4-ab associated disorders (p < 0.001). There were 17(M:F-8:9) patients with exclusive emesis in MOGAD in 58.8% pediatric age group, adults (35.3%) and late-onset (5.9%). ADEMON (acute demyelinating encephalomyelitis -ADEM followed by optic neuritis) was observed in 7 patients. Preceding clinical syndrome was ON (41.2%), brainstem syndrome (BS) (23.5%), involvement of both ON and BS in 23.5%, myelopathy (11.8%). MRI analysis showed combination of lesions affecting the brainstem (11), optic nerve (10), juxtacortical white matter (10) and periventricular lesions (3). Odds ratio for the presence of ADEM, lesions in medulla, pons, MCP or any of the three areas was found to be significant. Exclusive emesis without hiccups appears to be common in MOG-antibody associated disorder and may occur as a prodromal illness or exclusive clinical episode. It is known to occur most commonly in association with ADEM and/or Optic neuritis. [ABSTRACT FROM AUTHOR]

Abstract: Accumulating evidences suggest that dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) during ageing and in Parkinson''s disease (PD) is linked to neurodegenerative changes like exponential increase in α-synuclein expression and protein misfolding. Lewy body formation is also a quintessential observation in neurodegeneration and PD. In experimental models of PD, GRP78 a neuroprotective endoplasmic reticulum (ER) chaperone protein targets misfolded proteins for degradation and prevents release of caspase12 from the ER. Release of active caspase12 and its translocation to the nucleus induces ER mediated apoptosis. The effect of ageing on these proteins in human nigra is not known. We evaluated α-synuclein, caspase12, GRP78 and ubiquitin expression in the SNpc of Asian Indians, using immunohistochemistry and stereology. The number of α-synuclein and caspase12 immunoreactive neurons increased gradually with age whereas the number of GRP78-labeled neurons remained stable. In contrast, GRP78 protein expression was significantly upregulated with age, while α-synuclein and caspase12 increased slightly. An increase in the size and numbers of marinesco bodies was prominent after the sixth decade. The mild increase in α-synuclein expression and occurrence of marinesco bodies suggests ageing induced protein misfolding and GRP78 upregulation indicates presence of ER stress. The logarithmic upregulation of GRP78 could even be an indicator of neuroprotective or neuromodulatory response of ER to protein misfolding and initiation of unfolded protein response pathway. Since dopaminergic neurons are preserved in ageing Asian Indians, our study possibly signifies better proteasomal or ER response and partially explains the lower prevalence of PD in them. [Copyright &y& Elsevier]

Abstract: Glial derived neurotrophic factor (GDNF) protects dopaminergic nigral neurons and may prevent the progression of age-related motor deficits and Parkinson''s disease. The multi-component receptor complex which mediates the neuroprotective action of GDNF comprises of GDNF receptor alpha1 (GFRα1), a ligand binding cell surface component and RET receptor tyrosine kinase (RET) the signaling component. The expression of both these receptors in the normally aging human substantia nigra pars compacta (SNpc) needs to be studied since GDNF infusion is being considered for restoration of the lost nigrostriatal function. In the present study, we used unbiased stereology to quantify the number of GFRα1 and RET immunoreactive neurons in human SNpc from 28 weeks of gestation to 88 years (n =31). We further determined the levels of immunostaining intensity using densitometric image analysis to measure changes in levels of receptor expression. Here we report that human nigral dopaminergic neurons express GFRα1 and RET receptors at all ages. There was no reduction in the number of neurons expressing these receptors as a function of age. Moreover, there was no age-related decline in immunostaining intensity of both these receptors. It is likely that preservation of GDNF receptors in the nigral neurons is because these receptors are constitutively expressed in the human SNpc and thus it is GDNF responsive thru aging. The sustained receptor protein expression could also be another marker of preserved nigrostriatal function in Asian Indians. The latter possibility explains our earlier observation that the melanized nigral neurons are preserved with age in the Asian Indians. [Copyright &y& Elsevier]

Abstract: Central nervous system tuberculosis is still one of the leading causes of morbidity in the developing world, and tuberculous abscess is one of its uncommon manifesting forms. It closely mimics a pyogenic abscess clinically, radiologically, and histologically. An accurate diagnosis is imperative due to therapeutic implications. In this study, 21 cases of tuberculous abscesses encountered over a period of 13 years (1995–2007) were reviewed to study the clinical, radiological, and histopathological spectrum of the disease. The presence of palisading epithelioid cells and sheets of foamy histiocytes, enclosing a neutrophillic exudate rich in fibrin with nuclear debris, were clues as to suspicion of a tuberculous abscess. The demonstration of acid fast bacilli in the wall of the abscess or necrotic contents by microscopy or culture is essential to confirm the diagnosis of tuberculous abscess. A high index of clinical suspicion is necessary particularly in countries endemic for tuberculosis to ensure an accurate diagnosis and application of an appropriate therapy. [Copyright &y& Elsevier]

Abstract: Malignant peripheral nerve-sheath tumours (MPNST) with a rhabdomyomatous component are referred to as malignant triton tumours. Cervical tritons are rare, with only one previous report. We present a 28-year-old male patient with a malignant triton tumor involving the cervical spine with neurofibromatosis Type 1 presenting with symptoms of rapidly progressive cord compression. Radiology was suggestive of a MPNST with hemorrhage at the C2–C3 level. He underwent surgery with decompression of the intradural, and a small part of the extradural, component. To our knowledge this is the first report of a cervical triton tumor presenting with an intratumoral bleed. [Copyright &y& Elsevier]

Good visualization is a prerequisite for performing microvascular anastomosis. The most commonly used dye, methylene blue, has several limitations: it is washed off quickly and stains all the vessel layers. The objective of our study is to use 2 new novel dyes for improving visualization. After ethical committee approval, 2 Dyes (2% cresyl violet, 1% eosin) were studied in 3 groups, 20 rats in each group and 5 rats in the combined group. End-to-side anastomosis was performed in the classic fashion in 45 rats. After venotomy, the dye was applied to the raw surface of the vessels and subsequently, anastomosis was performed. The improvement in visualization was judged by 3 blinded experts and nonexperts in 4 groups on a scale of 1–10. Scores were statistically analyzed. After 2 weeks, animals were re-explored to check the delayed patency, and segments were harvested for histopathologic analysis. The immediate and delayed patency rates were 100% (45/45) and 97% (33/34), respectively. In statistical analysis, the combined group (P = 0.005)was judged statistically significant because of the contrast in color. All the layers were stained by both dyes, staining lasted until the end of the surgery. Visibility of the cut ends was better in cresyl violet. All histopathologic findings suggested normal changes at the anastomotic site. This study showed that the use of these 2 dyes was not only feasible but highly efficacious. Even though all the layers were stained by both the dyes, the visibility of the cut ends was better. In both dyes, staining lasted until the end of surgery. To the best of our knowledge, this is the first study that has used these 2 novel dyes to improve visualization in microvascular anastomosis in an experimental setting. [ABSTRACT FROM AUTHOR]

Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls. We performed a retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated. During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range [IQR] = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency. Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks. [ABSTRACT FROM AUTHOR]

Selective neuronal vulnerability (SNV) of specific neuroanatomical regions such as frontal cortex (FC) and hippocampus (HC) is characteristic of age-associated neurodegenerative diseases (NDDs), although its pathogenetic basis remains unresolved. We hypothesized that physiological differences in mitochondrial function in neuroanatomical regions could contribute to SNV. To investigate this, we evaluated mitochondrial function in human brains (age range:1–90 y) in FC, striatum (ST), HC, cerebellum (CB) and medulla oblongata (MD), using enzyme assays and quantitative proteomics. Striking differences were noted in resistant regions- MD and CB compared to the vulnerable regions- FC, HC and ST. At younger age (25 ± 5 y), higher activity of electron transport chain enzymes and upregulation of metabolic and antioxidant proteins were noted in MD compared to FC and HC, that was sustained with increasing age (≥65 y). In contrast, the expression of synaptic proteins was higher in FC, HC and ST (vs. MD). In line with this, quantitative phospho-proteomics revealed activation of upstream regulators (ERS, PPARα) of mitochondrial metabolism and inhibition of synaptic pathways in MD. Microtubule Associated Protein Tau (MAPT) showed overexpression in FC, HC and ST both in young and older age (vs. MD). MAPT hyperphosphorylation and the activation of its kinases were noted in FC and HC with age. Our study demonstrates that regional heterogeneity in mitochondrial and other cellular functions contribute to SNV and protect regions such as MD, while rendering FC and HC vulnerable to NDDs. The findings also support the "last in, first out" hypothesis of ageing, wherein regions such as FC , that are the most recent to develop phylogenetically and ontogenetically, are the first to be affected in ageing and NDDs. [Display omitted] • The processes contributing to region-specific selective neuronal vulnerability (SNV) and their accrual during aging is underexplored in human brains. • We noted that regional mitochondrial, antioxidant and synaptic heterogeneity based on expression and phosphorylation dynamics underlies the SNV of frontal cortex (FC) and hippocampus (HC) to neurodegeneration. • Expression and phosphorylation profile of microtubule associated protein tau (MAPT) and associated kinases during ageing in FC and HC, also probably contributes to SNV. • Regions that develop first [medulla oblongata (MD)] are defined by relatively high mitochondrial, metabolic and antioxidant function contributing to neuroprotection, compared to vulnerable areas such as FC, HC, and striatum (ST), that develop later, providing the biological basis for the "last in first out" hypothesis of ageing. [ABSTRACT FROM AUTHOR]

Age being a risk factor for Parkinson's disease, assessment of age-related changes in the human substantia nigra may elucidate its pathogenesis. Increase in Marinesco bodies, α-synuclein, free radicals and so forth in the aging nigral neurons are clear indicators of neurodegeneration. Here, we report the glial responses in aging human nigra. The glial numbers were determined on Nissl-stained sections. The expression of glial fibrillary acidic protein, S100β, 2′, 3′-cyclic nucleotide 3′ phosphodiesterase, and Iba1 was assessed on cryosections of autopsied midbrains by immunohistochemistry and densitometry. The glial counts showed a biphasic increase, of which, the first prominent phase from fetal age to birth could be physiological gliogenesis whereas the second one after middle age may reflect mild age-related gliosis. Astrocytic morphology was altered, but glial fibrillary acidic protein expression increased only mildly. Presence of type-4 microglia suggests possibility of neuroinflammation. Mild reduction in 2′, 3′-cyclic nucleotide 3′ phosphodiesterase–labeled area denotes subtle demyelination. Stable age-related S100β expression indicates absence of calcium overload. Against the expected prominent gliosis, subtle age-related morphological alterations in human nigral glia attribute them a participatory role in aging. [ABSTRACT FROM AUTHOR]

Rasmussen encephalitis (RE) is a rare, chronic, idiopathic, progressive, inflammatory, neurodegenerative disease process and typically seen in pediatric cohort. Although primarily a disease affecting children, adult cases with RE have also been reported. It manifests as drug refractory epilepsia partialis continua (EPC). Immunomodulation, although delays progression of disease, seldom influences outcome. Imaging is crucial for early diagnosis, and monitoring disease progression. Magnetic resonance imaging (MRI) is mainstay of imaging with nuclear imaging being a complimentary tool for diagnosing RE. Typical imaging features of RE on MRI are hemispherical atrophy, caudate nucleus atrophy, ex vacuo dilatation of the ventricular system and sulci. We review 5 cases of RE who fulfilled diagnostic criteria proposed by Bien et al. in 2005. One patient had typical imaging pattern of RE while other four patients had atypical imaging features of RE on PET-MRI. • Rasmussen encephalitis (RE) is a rare, chronic, idiopathic, progressive, inflammatory, neurodegenerative disease process and typically seen in paediatric cohort. • Although primarily a disease affecting children, adult cases with RE have also been reported. • It manifests as drug refractory epilepsia partialis continua (EPC). • Immunomodulation, although delays progression of disease, seldom influences outcome. • Imaging is crucial for early diagnosis, and monitoring disease progression. • Magnetic resonance imaging (MRI) is mainstay of imaging with nuclear imaging being a complimentary tool for diagnosing RE. • Typical imaging features of RE on MRI are hemispherical atrophy, caudate nucleus atrophy, ex vacuo dilatation of the ventricular system and sulci. • We review 5 cases of RE who fulfilled diagnostic criteria proposed by Bien et al. in 2005. • Our series represents a constellation of typical and atypical imaging findings in cases of RE. • While, early diagnosis is imperative, it is indeed a great challenge. • Knowledge of typical, atypical imaging findings ensures prompt early diagnosis. • A hybrid PET-MRI imaging adds value in suggesting a diagnosis of RE with subtle structural imaging findings or in the early stages of the disease, and helps identify biopsy targets. [ABSTRACT FROM AUTHOR]

Abstract: The equilibrium between antioxidant function and oxidative stress is implicated in brain pathology. However, human studies on oxidant and antioxidant markers rely on postmortem tissue that might be affected by pre and postmortem factors. To evaluate the effect of these variables, we tested whether antioxidant enzymes [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR), GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation) are affected in postmortem human brains (n =50) by increase in postmortem interval (2.5–26h), gender difference and agonal state [based on Glasgow coma scale (GCS): range: 3–15] in different anatomical regions-frontal cortex (FC), cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus (HC). While SOD and catalase activities were relatively unaltered, GR and GPx activities were affected by agonal state (GR in CB, p <0.05; GPx in MO, p <0.05) indicating altered GSH dynamics during the secondary events following neuronal injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level was decreased with PMI (MO, p =0.02) which could be partly attributed to increase in MDA levels with increasing PMI in MO (p <0.05). Total GSH level was higher in CB (p <0.017) and MO (p <0.04) in female brains compared to males. Interestingly, HC and SN regions showed significant stability in most of the markers tested. We suggest that while SOD and catalase were relatively unaffected by the pre and postmortem factors, GSH and its metabolic enzymes were significantly altered and this was more pronounced in MO of postmortem human brains. These data highlight the influence of pre and postmortem factors on GSH dynamics and the inherent differences in brain regions, with implications for studies on brain pathophysiology employing human samples. [Copyright &y& Elsevier]

Abstract: Background: Primary cardiac lymphoma is extremely rare in immunocompetent patients. Clinical manifestations vary, and, most often, diagnosis is not made until autopsy. The majority of reported primary cardiac lymphoma cases have been of B-cell origin, while T-cell cardiac lymphomas have been extremely rare. Occasionally, lymphomas and other systemic malignancies clinically present as paraneoplastic neurological syndromes. Methods: We report a unique case of primary cardiac peripheral T-cell lymphoma of cytotoxic phenotype, clinically presenting with neurological features of external ophthalmoplegia and lower cranial nerve paresis mimicking mitochondrial cytopathy, that was recognized at autopsy. Brain and thoracoabdominal viscera retrieved at autopsy were fixed in 10% buffered formalin and processed for paraffin embedding. In addition to routine histology, immunohistochemistry for immunophenotypic characterization of lymphoma cells was performed. Fresh skeletal muscle was processed for cryosectioning and histochemical staining. Results: On gross examination, the heart showed multiple circumscribed, whitish nodules on both sides. Histological examination of these nodules revealed lymphomatous deposits—cells expressing CD45, CD2, CD3, CD5, CD7, CD8, perforin, and granzyme B. Histological sections from the brain showed foci of demyelination and patchy perivascular lymphoid cell aggregates in leptomeninges and within the parenchyma. These lymphoid cells expressed CD2, CD3, and CD5, with the T cells being predominantly CD4 (CD4:CD8>2), which was unlike the CD8-predominant lymphomatous infiltrate in the heart. Hence, these lymphoid cells in the brain, rather than disseminated lymphoma cells, were considered to be related to the demyelinating process. There was no evidence of lymphomatous deposits in the rest of the viscera examined. Conclusion: A diagnosis of primary cardiac peripheral T-cell lymphoma of cytotoxic phenotype clinically manifesting as paraneoplastic demyelinating lesions in the brain was described. [Copyright &y& Elsevier]

The rare clinical entity of primary posterior pituitary tumors (PPTs) includes pituicytomas, granular cell tumors, spine cell oncocytomas, and sellar ependymomas. The recent World Health Organization classification of PPTs based on thyroid transcription factor 1 positivity has led to more investigations into the epidemiology, clinical presentation, nature history, histologic features, and operative characteristics of these tumors. The aim of this review is to summarize the characteristics of primary PPTs. Our summary involved an in-depth review of the literature on PPTs. Our systematic review was carried out using the PubMed database and PRISMA guidelines. An initial search identified 282 publications. After strict application of the inclusion criteria, we found 16 articles for case series of patients with primary PPT (N > 5), which were included in our table for literature review. An additional 10 articles were review articles on PPTs published in the last 20 years and were used as resource for our systematic review. An extensive analysis was then performed to extract relevant clinical data with respect to the clinical radiologic histopathologic profile of primary PPTs and their treatment outcome. Primary PPTs are a rare group of pituicyte-derived low-grade nonneuroendocrine neoplasms that arise from the sellar region. The nondescript radiographic findings and subtle endocrine abnormalities also veil their accurate diagnostic prediction. As shown through the narrative as well as the literature review, there is still a lot to be understood about PPTs. A prospective multicenter registry of these rare tumors would benefit both the neurosurgical as well as the endocrinologic knowledge base. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis of the central nervous system, a saprophytic infection with a unique vascular tropism, carries the burden of increased morbidity and mortality. Early clinical and imaging findings can masquerade as an innocuous condition before a secondary inexorable progression. We highlight the clinical and imaging phenotype of a patient with fatal invasive granulomatous aspergillosis. A 39-year-old man presented with progressive weakness of the left upper and lower limb for 4 months. Imaging demonstrated right holohemispheric extensive, numerous, confluent, ill-defined, T2 hypointense foci with moderate perilesional edema. Numerous foci of microhemorrhages with cortical asymmetric mineralization were seen. Post-contrast heterogeneous, variegate, punctiform enhancement of the lesions was observed extending to the ventricular margins. Volume loss of the left cerebral peduncle and ipsilateral long white matter descending tracts was noted. Histopathologic examination of a stereotactic biopsy specimen from the frontal region lesion showed dense inflammatory infiltrate with granulomas, a few in a perivascular distribution and branching septate hyphae resembling Aspergillus. The patient was initiated on antifungal therapy and in the following week, he had progressive drowsiness. The patient succumbed the next day. Diffuse holohemispheric, progressive presentation of a granulomatous form of invasive aspergillosis is a rare entity. The miliary pattern of heterogenous enhancement, holohemispheric conglomerate T2 hypointensities, interspersed hemorrhage, juxtacortical punctate T2 hyperintense foci, low perfusion, and the relative absence of diffusion abnormality are distinctive features. Early diagnosis of this atypical imaging phenotype of Aspergillus infection and appropriate treatment is critical for better prognosis. [ABSTRACT FROM AUTHOR]

Vascular tumors of the spine range from benign hemangiomas to malignant angiosarcomas. Hemangioendotheliomas of spine are tumors of intermediate-grade malignancy with rare occurrence in the intradural location. The imaging and histopathologic features may mimic other common lesions occurring at this location. A 70-year-old woman presented with lower limb weakness and sensory impairment along the L5–S1 dermatome. A radiologic diagnosis of neurofibroma at the intradural location of the L4–L5 level was made, and total excision of the space-occupying lesion was done. Histopathologic examination, however, revealed a vascular tumor consistent with hemangioendothelioma, which was confirmed by immunohistochemical analysis. We present this case discussing the dilemmas and difficulties in arriving at the diagnosis, highlighting the role of immunohistochemical aid. Histomorphology, aided by ancillar tests like immunohistochemistry, remains the criterion for the definitive diagnosis of such rare lesions, and pathologists need to be aware of these lesions occurring in uncommon locations. [ABSTRACT FROM AUTHOR]

Introduction Actinomycosis is an uncommon chronic suppurative infection that rarely affects the central nervous system (CNS). It is caused by filamentous Gram-positive anaerobic bacteria that is a normal commensal but causes suppurative and granulomatous inflammation after disruption of anatomical barriers. We report the largest series of 17 histologically confirmed cases of CNS actinomycosis and review clinical, imaging, and histopathologic features. Methods All histologically confirmed cases of CNS actinomycosis diagnosed between January 2010 and June 2016 were retrieved from the neuropathology records. The demographic profile, clinical, radiologic, microbiologic, and histologic features, treatment, and clinical outcomes were reviewed. Results Seventeen cases were histopathologically diagnosed to have CNS actinomycosis. Nine of these were primarily admitted and managed in our institute, whereas the remaining 8 were referred to us for histopathologic diagnosis. Mean age at presentation was 31.4 years, with male predilection (3.25:1). Mean duration of symptoms was 2.95 months. Systemic symptoms were noted in 5 patients, although no systemic focus was detectable. Pachymeningitis was most common type (9; 52.94%), and chronic abscess was identified in 7. History of previous surgery for osteomyelitis was forthcoming in 3. All patients underwent surgical excision/aspiration of the lesions. Histologically, lesions revealed characteristic suppurative granulomatous response with giant cells and actinomycotic colonies were detected within necrotic centers. Cultures failed to grow Actinomyces in all. Follow-up data were available in 9 patients managed in our institute, and all had good outcomes at the median follow-up period of 32 months after antibiotic treatment for mean period of 8.4weeks. Conclusions Histopathology remains the cornerstone for diagnosis of actinomycosis as on culture confirmation is very rare. [ABSTRACT FROM AUTHOR]

Objective: Papillary glioneuronal tumors (PGNT) are a rare and recently recognized tumor entity. The neuroimaging findings were reviewed to determine if any specific findings emerge to assist a preoperative diagnosis of PGNT.Materials and Methods: Seven histologically confirmed cases of PGNT were evaluated from 2004 to 2014. Clinical, neuroimaging and histological findings were reviewed and tabulated.Results: Headache and seizures were observed in 4 patients (57.1%) each. The majority (n=5, 71.4%) of lesions were periventricular and located in temporal lobe with 57.1% cases being solid cystic (n=4), and 42.9% being purely solid (n=3). Calcification and hemorrhage were noted in 3 cases (42.9%) and 5 cases (71.4%) respectively. The most frequent imaging feature was the presence of septations in the cystic component that enhanced on contrast which correlated with long pseudopapillary projections into the cyst cavity on histopathology. The solid inner component demonstrated heterogeneous enhancement. One case with tumor recurrence demonstrated hemorrhage with superficial siderosis, patchy diffusion restriction, raised choline and focal areas of raised perfusion which correlated on histopathology with increased cellularity and anaplasia.Conclusion: Presence of cystic mass in periventricular location with septations and a solid inner component should raise a suspicion of PGNT on neuroimaging. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii ( T.gondii ) infection can be devastating in the immunodeficient causing high morbidity and mortality. Due to limited availability of both diagnostic facilities and Highly Active Antiretroviral Therapy (HAART), toxoplasmosis continues to be a significant problem amongst Acquired Immuno Deficiency Syndrome (AIDS) patients in India. While scanty literature is available on T. gondii isolates in animals in India, little is known about the genetic diversity of the parasite in humans. Therefore, the present study investigated the genetic diversity of T. gondii in 25 confirmed cases of cerebral toxoplasmosis developing on the background of human immunodeficiency virus (HIV) infection/AIDS. PCR DNA sequencing was performed at four important genetic loci of T. gondii : BTUB, GRA6, alternative SAG2 (alt SAG2) and SAG3 on DNA from tissues obtained at postmortem. The amplified products from all the cases were successfully sequenced except at one locus for one case. Results of the present study suggest that majority of the patients (22/25; 88%) in South India are infected with strains that are recombinants of type II/III and/or strains representing T. gondii different from the archetypal lineages I, II, and III. In addition, clonal types III, MAS, and MAS variant genotypes were encountered. No clonal type I or II was seen in the present study. In addition, variants were observed at alt SAG2 and SAG3 but BTUB and GRA6 were highly conserved. Single nucleotide polymorphisms were observed mainly at two loci which are coding for surface antigens at alt SAG2 and SAG3. In conclusion, the present study reveals genetic diversity in India amongst strains of T. gondii from clinical cases of toxoplasmosis which is in accordance with other recent studies showing a high rate of genetic diversity in this parasite across the globe. There is a need to genotype T. gondii from different forms of toxoplasmosis in humans in India. [ABSTRACT FROM AUTHOR]

Objectives Patients with scrub typhus often complain of myalgia, but a comprehensive study on muscle dysfunction is lacking. We therefore report the clinical, electromyographic and muscle biopsy findings in patients with scrub typhus. Methods Consecutive patients with scrub typhus were included, and their clinical and laboratory findings were noted. The patients with myalgia or weakness and elevated serum creatine kinase (CK) were considered to have muscle involvement. Electromyography (EMG) and muscle biopsy were done in some patients. Patients were treated with doxycycline 200 mg daily for 7 days, and their clinical and biochemical outcome on discharge and one month were evaluated. Results 13 out of 33 (39.4%) patients had muscle involvement and their CK levels ranged between 287 and 3166 (859 ± 829) U/L. EMG revealed short duration polyphasic potentials, and muscle histopathology revealed evidence of vasculitis. There were significant correlations between severity of weakness and CK levels (r = − 0.6; p < 0.001), platelet counts (r = 0.4; p = 0.04), duration of illness (r = − 0.4; p = 0.01) and disability on discharge (r = − 0.4; p = 0.04). Patients with muscle involvement had more severe illness evidenced by a lower Glasgow Coma Scale score (p < 0.001), thrombocytopenia (p = 0.05) and greater disability on discharge (p = 0.007), when compared to those without muscle involvement. All the patients had complete recovery following doxycycline therapy, and CK levels also normalized. Conclusion Muscle dysfunction was present in 39% patients with scrub typhus. Although muscle histopathology showed evidence of vasculitis, patients responded to doxycycline. [ABSTRACT FROM AUTHOR]